An electrostatic energy-based charge model for molecular dynamics simulation

Abstract

The interactions of the polar chemical bonds such as C=O and N-H with an external electric field were investigated, and a linear relationship between the QM/MM interaction energies and the electric field along the chemical bond is established in the range of weak to intermediate electrical fields. The linear relationship indicates that the electrostatic interactions of a polar group with its surroundings can be described by a simple model of a dipole with constant moment under the action of an electric field. This relationship is employed to develop a general approach to generating an electrostatic energy-based charge (EEC) model for molecules containing single or multiple polar chemical bonds. Benchmark test studies of this model were carried out for (CH3)2-CO and N-methyl acetamide in explicit water, and the result shows that the EEC model gives more accurate electrostatic energies than those given by the widely used charge model based on fitting to the electrostatic potential (ESP) in direct comparison to the energies computed by the QM/MM method. The MD simulations of the electric field at the active site of ketosteroid isomerase based on EEC demonstrated that EEC gave a better representation of the electrostatic interaction in the hydrogen-bonding environment than the Amber14SB force field by comparison with experiment. The current study suggests that EEC should be better suited for molecular dynamics study of molecular systems with polar chemical bonds such as biomolecules than the widely used ESP or RESP (restrained ESP) charge models.